This application seeks support for years 26-30 of a T32 grant for post-doctoral research training for MD, PhD and MD/PhD scientists. The training centers in the Department of Pathology and Immunology at Washington University. We have a faculty of 29 distributed among seven departments, but with highest representation in Pathology and Immunology. The faculty is made up of a highly collegial group of immunologists and cell/molecular biologists who have interacted heavily for several years. The research of much of the faculty is on various aspects of immunology and host resistance, but also includes heavy emphasis on the molecular basis of cell activation (for example our projects focus on host responses to tumors and viruses, lymphocyte differentiation and activation, cell biology and biochemistry of antigen processing, the molecular basis and analysis of cell interaction molecules, regulation of DNA cycle). There are two types of trainees-(a) those with either MD or MD/PhD degrees who seek a serious, in- depth experience in research following their clinical training in Pathology or (b) fellows with a graduate or MD degree, not associated with Pathology clinical training, who have an interest in the research done by any of the faculty members: we have a yearly applicant pool of about 200 qualified individuals who compete for a total of 80 postdoctoral slots among the 29 laboratories. Of these, ten/year are supported by this training grant. We request renewal of our ten training positions. A Steering Committee of 6 senior faculty members oversees the training and is responsible for the selection of trainees. Training includes a 2-3 year period of full-time laboratory research, where the trainee is exposed to the latest approaches in cell and molecular biology (e.g., transgenic and knockout mice, peptide chemistry, DNA technology). Part of the training includes laboratory meetings and reports, participation in weekly seminars, training in research ethics and opportunities for courses in Cancer Biology. Of the 53 trainees that have been supported by this Program in the last 10 years, 98% continue in research. Forty-seven percent of our trainees supported during the last 10-year period are still in training while 53% have completed the program. Of the latter, 78% hold faculty positions, mostly in Pathology. This successful training program is thus producing the next generation of basic and clinician scientists who will elucidate many of the heretofore unknown mechanisms that lead to cancer development and/or discover novel therapeutic strategies that can be used to treat neoplastic disease.